Analysis of Methylated Genes in Peritoneal Fluids of Ovarian Cancer Patients: A New Prognostic Tool

Abstract

Epithelial ovarian cancer causes more deaths in the United States and Europe than any other cancer of the female reproductive organs. The latest cancer statistics indicated an estimated 25 400 new cases of ovarian cancer and 14 300 deaths in the United States (1). The primary treatment for early-stage ovarian cancer is surgery, which in theory could be curative in low-risk patients whose disease is limited to the ovaries. The relative importance of prognostic factors such as tumor grade, histologic cell type, and other factors for defining individuals at low risk of recurrence is unknown (2). Cytologic examination of peritoneal fluids forms part of the staging process for ovarian cancer and influences therapeutic interventions (3). It is known that regardless of International Federation of Gynecology and Obstetrics (FIGO) stage, positive peritoneal washing cytology predicts poor prognosis for women with epithelial tumors of the genital tract, except for patients with borderline ovarian tumors (4). Because of the diagnostic pitfalls entailed in the cytologic examination of peritoneal washings (5), some additional methods for peritoneal fluid diagnosis have been tested, including flow cytometric DNA analysis (6) and a telomerase assay (7)(8). Changes in the status of DNA methylation, known as epigenetic alterations, are among the most common molecular alterations in human neoplasia (9)(10), including ovarian cancer (11)(12)(13). Moreover, it is now widely known that methylated DNA can be detected in various body fluids and that the methylation status of some genes can be used for risk assessment of various types of human neoplasia [summarized in Ref. (14 …